CLINICAL-STUDIES OF HUMAN PANCREATIC-ENZYME SYNTHESIS

Very little is known of the effects of diet and disease on panceratic enzyme syntheis in humans as conventional tests measure the secretory response to secreagogues, such as CCK, and secretion may be unrelated to synthesis because of the masking effect of a large intracellular po ol of stored enzymes (zymogens). In order to obtain information on enz yme synthesis, as well as secretion, we have measured the incorporatio n characteristics of isotopically labelled amino acids (e.g., C-14 or C-13 leucine tracer) into amylase and trypsin protein, extracted by af finity chromatography from duodenal secretions during pancreatic stimu lation with CCK-8. The results of our studies in healthy volunteers an d patients have suggested that (a) it takes between 75 and 101 min for the participation of newly synthesized pancreatic enzymes in the dige stive process, and that zymogen stores are replaced at a rate of betwe en 12 percent and 47 percent per hour in normal healthy subjects, (b) the synthesis and production rates of trypsin and amylase are parallel in healthy subjects, but can diverge under stressful conditions such as hypersecretory states, post-acute pancreatitis and protein malnutri tion, (c) hyperphagia stimulates the synthesis of enzymes whilst malnu trition diminishes the synthesis of trypsin to a greater extent than a mylase, (d) intravenous glucose and amino acids exert negative feedbac k control on the synthesis and release of amylase and trypsin, and (e) the decreased secretion of pancreatic enzymes in Type 1 insulin-depen dent diabetics is more a consequence of defective enzyme release from zymogen stores than defective synthesis. In conclusion, our results in dicate that changes in pancreatic enzyme secretion noted in patients d o not always reflect changes in enzyme synthesis, and that the product ion of individual enzymes may diverge under certain circumstances. Bas ed on the methodology described, it shoud be possible to develop more sensitive clinical tests of pancreatic function that provide informati on not only on the abiltiy of the pancreas to secrete enzymes under ce rtain disease states, but also information on the gland's synthetic ac tivity.